A New Drug Target in Allergic Diseases: Bruton Tyrosine Kinase

Though first recognized as a signaling molecule in B cells, Bruton tyrosine kinase (BTK) has been shown to play a crucial role in signal transduction in innate and adaptive immune cells. BTK is an attractive therapeutic target, given its diverse role in immune regulation. Development of the first-generation BTK inhibitor (BTKi), ibrutinib, revolutionized the treatment of B-cell malignancies. Since its approval, newer-generation BTKis with improved pharmacological properties have been developed, with higher selectivity for BTK and fewer off-target effects than ibrutinib. BTK is essential for IgE-driven allergic responses and may influence IgE antibody production by B cells. Activation of BTK via the high-affinity Fc receptor for IgE, FcεRI, results in mast cell and basophil degranulation and release of histamine and other inflammatory mediators. BTKis are a potential novel therapeutic option in patients with mast cell-driven autoimmune and allergic diseases. This review summarizes the current evidence for BTK in urticaria (chronic spontaneous and chronic inducible urticaria [CSU/CIndU]), asthma, food allergy, and atopic dermatitis (AD). It also highlights the efficacy of BTKis in urticaria and allergic diseases where FcεRI/IgE is the pathogenic target. Based on limited available data, BTK does not seem to have a prominent role in the pathogenesis of AD, and its role in asthma is unclear, thus necessitating further clinical research. Remibrutinib and rilzabrutinib have shown the most promise in allergic and autoimmune diseases to date; remibrutinib is approved in adults with CSU, and rilzabrutinib is approved in adults with persistent or chronic immune thrombocytopenia.